During the 1930s, Morris helped a number of German and Austrian philosophers immigrate to the United States, Rudolf Carnap in particular; they were colleagues from 1936 to 1952. Morris was involved in the Unity of Science movement, and was Associate Editor of the International Encyclopedia of Unified Science. He was close to the Vienna Circle and its logical positivism, and developed an original form of pragmatism. At the same time, he wrote poetry and called for new forms of religious belief.

Morris's approach to semiotics divided the subject into syntax, semantics, and pragmatics. He proposed a threefold division of a sign into a sign vehicle, designatum, and interpreter; this trichotomy first appeared in his book Foundations of the Theory of Signs. A semiotics structured in this manner would appear to owe much to Charles Peirce. Yet some Peirceans have accused Morris of reading Peirce superficially, through the distorting lens of Morris's behaviorism. While Peirce envisioned a semiotic philosophy based on universal categories of perception and the assumption that "every thought is a sign", Morris wanted to develop a science of signs "on a biological basis and specifically with the framework of the science of behavior". His students include the semiotician Thomas Sebeok.